A major need in immunogenetic studies are fast, reproducible and sensitive methods for amino acid sequence analysis of proteins. Mass spectrometric (MS) techniques provide a promising means of meeting these goals. Methods under study involve enzymatic digestion of polypeptides into dipeptides using either dipeptidyl aminopeptidase or dipeptidyl carboxypeptidase (DAP/DCP method) and use of MS for rapid identification of dipeptides produced. Another employs direct introduction of larger derivatized peptides into the MS for analysis (DI method). Computer assisted data analysis programs for both MS methods are under development. The DAP/DCP and DI methods are being tested using rabbit and mouse heavy chains as model proteins because these proteins are not readily amenable to routine sequence analysis techniques. The structure of rat beta-2 microglobulin is also under study using this method.